Encapsulated active material immobilized in hydrogel microbeads

ABSTRACT

A microbead comprising a hydrophilic matrix having active-filled microcapsules entrained therein. Compositions comprising the microbeads suspended in solution are useful for delivering active material. The microbeads of the invention may be controllable by exposing the microbeads to high or low humidity or moisture.

FIELD OF THE INVENTION

The invention relates broadly to a combination of encapsulation,immobilization and release of active material using hydrogel microbeads,where the active can be either water soluble or water insoluble.Specifically, the hydrogel microbeads immobilize encapsulatedagricultural chemicals such as pheromones, herbicides, insecticides andpesticides, whereby the encapsulated active material is released intoambient air by diffusion through at least two paths sections: amicrocapsule shell and a hydrophilic matrix.

BACKGROUND

Methods of eliminating unwanted pests from orchards, crops and forestsfrequently entail the use of organophosphate insecticides. Alternativemethods involve insect mating disruption, where insect pheromones areused to control pests and protect agricultural crop. In insect matingdisruption methods, the mating pheromone plume of a female insect istypically masked with other pheromone point sources. This reduces thelikelihood of a male insect finding a female, and subsequently disruptsand reduces larvae production. The insect population of the nextgeneration is thus decreased, as well as potential crop damage.

Conventional sprayable pheromone formulations are generally provided inliquid filled microcapsules containing an active. Typically, themicrocapsules have a polyurea membrane that can be formed using aninterfacial process involving an isocyanate and an amine.Microencapsulation by this method has been described for example in U.S.Pat. No. 4,487,759 (Nesbitt et al, 1984). These polyurea membranes allowactives to be released into the atmosphere for up to a total of 2-3weeks for most insect pheromones. Membranes of polyurea capsules aregenerally semi-permeable, therefore active material can diffuse acrossthe membranes and release slowly with time. Potentially, highconcentrations of active in the air can be observed immediately upondelivery or spraying of encapsulated products. This may be attributableto a high occurrence of capsule bursts or potential leaks inmicrocapsules.

U.S. Pat. No. 4,532,123 teaches capsules containing a pharmaceuticalactive material in primary capsules, that are further encapsulatedwithin a second membrane to create secondary capsules. The intracapsularliquid core of the secondary capsules contain enzymes which slowlyhydrolyze the membrane of the primary capsules. This slow hydrolysisenables the slow release of active from the primary capsules into thelarger capsular core for controlled delivery.

A Japanese paten, JP 8-173794 teaches encapsulation of an amine withinsmall capsules of polymethyl methacrylate membranes. These capsules arefurther encapsulated within an epoxy-amine polymeric shell. Similarly,the amine within the tiny capsules is released into the core of thelarger capsule ultimately delivering the amine upon rupturing of thepolymeric shells.

Use of interfacial condensation to encapsulate substances such aspharmaceuticals, pesticides and herbicides is taught in U.S. Pat. No.3,577,515. The encapsulation process involves two immiscible liquidphases (typically water and an organic solvent), one being dispersed inthe other by agitation, and the subsequent polymerization of monomersfrom each phase at the interface between the bulk (continuous) phase,and the dispersed droplets. Polyurethanes and polyureas are materialssuitable for producing the microcapsules. The microcapsules comprising apolymeric sphere and a liquid centre, ranging from 30 micron to 2 mm indiameter, depending on monomers and solvents used.

Highly viscous and thickened hydrogels have been used to deliverpheromones, fragrances and other non-water soluble actives. U.S. Pat.No. 4,755,377, for example, describes a process of encapsulating perfumeor fragrant material within an aqueous-based gel composition. Theresulting material is in the form of a highly viscous semi-solid. U.S.Pat. No. 5,645,844 describes the use of chitosan paste for delivery ofpheromones to disrupt insect mating, where the material can be dispensedby an apparatus such as a caulking gun. Due to their thickness and highviscosity, these materials, however, are generally unsprayablecompositions.

Most hydrogels are safe and non-toxic to humans. Hydrogels have beenused for the encapsulation of biological materials whereby theformulation is non-lethal to the viability of the cells, proteins, andrelated materials. U.S. Pat. No. 4,689,293, describes the process ofencapsulating living tissue or cells. The encapsulation shell permitsthe passage of materials and oxygen to the cells and permits thediffusion of the metabolic by-products from the gel.

SUMMARY OF THE INVENTION

To provide an extended release period of an active, microbeadscomprising a hydrophilic matrix with active-filled microcapsulesentrained therein is provided. The hydrophilic matrix is capable ofimmobilizing a broad spectrum of microencapsulated active materials,either water soluble or non-water soluble. The microbeads may besuspended in a sprayable solution.

In an aspect of the invention, the hydrophilic matrix may be made from awater soluble matrix-forming material to provide an environmentallyfriendly microbead.

In a further aspect of the invention, the microbeads may be capable ofrehydrating after an initial dehydration and release of active. Thus,the release and longevity of the active can be controlled by adjustingthe humidity of the environment in which the microbeads have beendelivered.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a digital image of a light micrograph of a preferredembodiment (Example 3) of the invention, taken at 40× magnification.

FIG. 2 is a digital image of a light micrograph of another preferredembodiment of the invention (EXAMPLE 5), prior to dehydration, taken at40× magnification.

FIG. 3 is a digital image of a light micrograph of the same sample ofFIG. 2, after dehydration, taken at 40× magnification.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

It would be advantageous to provide a delivery system that can minimizeshell rupturing of active-filled microcapsules, to delay and/or prolongthe release of active materials. In view of the increasing awareness ofinsecticide toxicity to humans and other environmental concerns, itwould be advantageous to provide an active delivery system having anextended release life and having a hydrogel material in order that it benon-toxic and bio-degradeable. It would also be advantageous to providea system for sprayable, long-lasting active material delivery that wouldbe applicable to a broad spectrum of actives thereby eliminating theissue of reactivity of the active with one of the membrane components.

The present invention involves immobilizing encapsulated active(s)material within a hydrogel matrix, where the immobilization is providedin a protective microbead format. The microbeads can be suspended in asolution to provide a deliver system for active materials, where thesystem is capable of providing extended release periods. The matrixprovides physical protection to the microcapsules from externalpressures such as those that can occur during a spray delivery, forexample. This in turn, minimizes pre-mature capsule bursts (rupturing)and prolongs the release period of the active(s). Upon dehydration ofthe water from the hydrophilic matrix, the microcapsule containing theactive material remains immobilized within the residual matrix. Theactive is able to then release into the desired environement bydiffusion through the capsule shell or membrane, followed by diffusionpast or through the hydrophilic matrix.

The microbeads of the invention comprise a matrix forming material, andis preferably substantially spherical. The matrix forming materials ofthe present invention are hydrophilic and water soluble. Entrained orfinely dispersed within the matrix are microcapsules containing activematerial. Active materials that can be encapsulated and and thenimmobilized within the hydrogel microbeads include aldehydes, esters,alcohols, epoxy compounds, ethers, ketones, or combinations thereof.This invention is particularly advantageous for delivery of reactiveketones in which the double bond of the carbonyl group is conjugatedwith one or more double bonds, for example acetophenone where thecarbonyl group is conjugated with double bonds of the aromatic ring.

Conventional active delivery systems (such as for delivery of pheromone)generally involve polyurea or polymethyleneurea encapsulation, whereinterfacial polymerization or in situ polycondensation occurs to providemicroencapsulated products, respectively. These systems however, aretypically limited to encapsulation of water non-soluble and/ornon-alcohol active materials, due to, for example, the reactivity ofalcohol with the isocyanate contained in the polyurea membrane. Thepresent invention provides microbeads having matrix cores that canprovide sufficient immobilization of oil soluble actives and alcoholactives such that the active can be delivered and sprayed byconventional techniques. The hydrophilic matrix preferably andadvantageously imparts the capability of the hydrogel microbeads toimmobilize oil-soluble and alcohol active materials and minimizes therisk of undesired reactivity between the active and its immobilizer.Thus, immobilization of active materials by use of the microbeads of theinvention does not render the immobilized material inert or ineffective.

A further benefit from immobilizing active ingredients in hydrogelmicrobeads is the ability of the hydrogel to “swell” under humidconditions and shrink under dry conditions. As used herein, “swell” isdescriptive of the behavior of a microbead, wherein the size (volume) isenlarged (increased) due to absorption of water. This is likely due tothe hydrophilic nature of the matrix forming materials used toimmobilize the active material.

In the presence of humidity, the hydrogel microbeads are preferablycapable of absorbing moisture, rehydrating, and consequently releasingactive material contained within the matrix. This behavior can becyclical. Thus, by controlling the humidity (or dryness) of the ambientair, the release rate of active material from the microbeads can becontrolled such that specific periods of release can be generallypredicted. It is therefore possible with the present invention torelease the active material on demand from the microbead. Release ondemand, or “smart release,” can be advantageous in those instances whererelease is preferred at certain times. The microbeads' ability tofurther release active from the matrix and may increase the longeveityof releasing effective amounts of active material. Preferably, themicrobeads are delivered to an intended environment in effective amountsto obtain the desired effect. For example, microbeads having pheromonesentrained therein, are preferably delivered to a desired area in amountssuch that mating disruption is effected and release is accomplished formore than 4 weeks, more preferably, the microbead can release for morethan about 6 weeks; and most preferably more than about 8 weeks.

During the drying process (i.e dehydration) a surface film layer willform as a result of water evaporation from the hydrophilic matrix. Bothinitially and during use, the microbeads are characterized by a largesurface area to volume ratio, which helps maintain the rate of diffusionof the active material during use. Thus, it has been found thatmicrobeads made according to the method of present invention provideexcellent delivery systems as they are capable of releasing activematerial for extended periods. Furthermore, since the active isdispersed within a water-based matrix, additional protection fromenvironmental conditions (i.e., UV) can be provided.

Although it has been found that microbeads of the invention can be madehaving a diameter of up to about 5 millimeters (mm), it is preferredthat the microbeads be between about 1 micrometers (μm) to about 1000 μmand more preferably between about 1 μm to about 500 μm in diameter toensure that the microbeads are easily sprayable from conventional spraynozzles. Most preferably, to ensure minimal clogging in conventionalnozzles, the microbeads are less than about 400 μm in diameter. It isconceivable, however, that with the advent of larger spray nozzles notcurrently used in the industry, the microbeads can be provided in muchgreater diameters.

For, spraying applications, particularly aerial spraying, it isdesirable that the microbeads be capable of remaining suspended insolution (water) to ensure that the microbeads do not sink, settle, orcoagulate in the suspension. This also ensures an even spray coverage.Preferably, the microbeads of the invention are able to remain insuspension, thus minimizing if not eliminating the need to agitateduring application and optionally, during storage. Various suspensionaids can also be included in the suspension containing the microbeads ofthe invention. Examples of suitable suspension aids include rhamsam gum,xanthum gum, gellan gum, pectin, and gum arabic.

Owing to the handling to which the microbeads are subjected, it isdesirable that the microbeads of the present invention should besomewhat elastic, and not frangible. For example, atomization of asuspension during a spray application may force the suspension throughtwo rotating perforated discs that are immediately upstream of thedischarge nozzle. Sufficient elasticity of the microbeads minimizesphysical damage to the microbeads as they pass through the discs.

The microbeads of the present invention comprise a matrix formingmaterial and active material. Referring now to FIG. 1, microbeads 14 ofa preferred embodiment is shown, where a plurality of active-filledmicrocapsules 10 are entrained within hydrophlic matrix 12. As seen inFIG. 1, microcapsules 10 containing active material are preferablylocated between and within hydrophilic matrix 12, where matrix 12provides an immobilizing network around the droplets. The degree andextent of agitation as well as the type of surfactant used to form themicrobeads can affect the size and the dispersity of microcapsuleswithin microbead's matrix. Entrained microcapsules 10 are preferablybetween about 0.01 nm to about 300,000 nm in diameter. More preferably,the microcapsules are between about 0.5 nm to about 200,000 nm indiameter.

The matrix-forming material useful in the present invention arebiocompatible, water-soluble, have pendant functional groups, andcomplex with ions (e.g., polyvalent cations and/or anions) to formhydrogels. Functional groups of the matrix forming material include forexample, carboxyls, hydroxyls, primary or secondary amines, aldehydes,ketones, esters, and combinations thereof. Preferably the hydrophilicmatrix-forming material can be made from naturally occuringpolysaccharides, such as alginates, chitosans, gums, agars,carrageenans, or the matrix can be made synthetic, water solublemonomers, oligomers or polymers, such as, for example, polyvinylalcohol, poly(N-isoproylacrylamide), acrylamides, acrylates, andmethacrylates, or combinations thereof.

Suitable naturally occurring polysaccharides include the water-solublesalts of alginic, pectic and hyaluronic acids, the water-soluble saltsor esters of polyglucuronic acid, polymanuronic acid, polylygalacturonicacid and polyarabinic acid, and gum kappa-carrageenan. The preferredpolysaccharides are the ammonium, magnesium, potassium, sodium and otheralkali metal salts of alginic acid, and the most preferredpolysaccharide is sodium alginate.

“Alginate” is the general name given to alginic acid and its salts.Alginates are composed of D-mannosyluronic (mannuronic—“M”) andL-gulopyranosyluronic (guluronic—“G”) acid residues. The alginate usedto immoblize active droplets should be carefully selected to ensureproper microbead formation, ensure the stability of the microbeadsduring storage and delivery applications, and ensure that the microbeadsare able to shrink and swell appropriately to deliver the desired activematerial over an extended period of time (preferably 4-6 weeks).Preferably, an alginate is chosen such that the matrix formed issufficient in strength to withstand the shear forces (conditions) placedupon the microbeads during application via a spray nozzle—i.e., themicrobeads are resistant to rupture during the spray application.

For strength and stability of the microbeads, it is desirable to choosethe molecular weight and M:G ratio of the alginate to obtain preferredproperties of the ultimate matrix. Although alginates high in mannuronicacid are generally useful for thickening applications, whereas alginateswith a high level of guluronic acid are often used for forming gels,both alginate categories (individually or a mixture thereof) aresuitable for the microbeads of the invention. A preferred alginate thatimparts strength and rupture resistance is an alginate that has a highlevel of guluronic acid, e.g., greater than about 30 percent by weight.Alginate compositions with excessive levels of mannuronic acid couldresult in less stable and less rigid microbeads than high guluronic acidgels. However, high mannuronic acid alginates impart to the microbeadsthe capability of swelling and absorbing more water than microbeads ofhigh guluronic acid content. Thus, a careful balance of the advantagesimparted by each of M and G residues should be considered when choosinga suitable alginate.

Preferably, alginates used in the microbeads of the invention have amolecular weight in the range of about 100,000 kg/mol to about 2,500,000kg/mol, more preferably about 200,000 kg/mol to about 1,500,000 kg/mol.Furthermore, the alginates preferably have an M:G ratio in the range ofabout 0.2 to about 3.5; more preferably about 0.3 to about 1.85.

Preferred alginates have a high level of guluronic acid, for example arealginates from the algae Laminaria hyperborea, stem, whole plant orfrond. Preferred alginates with high levels of mannuronic acid includeAscophyllum nodosum, for example.

Gel matrices formed by crosslinking polysaccharides bearing pendantcarboxylate groups are also useful in the present invention. Thesecompounds are composed of water-insoluble alginates which include, withthe exception of magnesium and the alkali metal salts, the group IImetal salts of alginic acid. The water-insoluble alginate gels aretypically formed by the chemical conversion of water-soluble alginates,in an aqueous solution, into water-insoluble alginates. This conversionusually is accomplished by the reaction of a water-soluble alginate withpolyvalent cations released from a soluble di- or trivalent metal salt.

Water-soluble alginates can include the ammonium, magnesium, potassium,sodium, and other alkali metal salts of alginic acid. Water-insolubledi- or trivalent metal salts suitable for the present invention shouldsatisfy two requirements: (1) that the water-insoluble metal saltcontain a di-or trivalent metal ion capable of complexing with thependant carboxylate groups of the water-soluble polysaccharide to causethe formation of a water-insoluble polysaccharide gel; and (2) that thewater-insoluble metal salt reacts with a water-soluble acid to form awater-soluble metal salt.

A common and suitable alginate gel is composed of calcium aliginate.

Sources for the crosslinking calcium ions used in the formation ofalginate gels include, for example, calcium carbonate, calcium sulfate,calcium chloride, calcium phosphate, calcium tartrate, calcium nitrate,and calcium hydroxide. Other acceptable crosslinkers may includelanthanum chloride, ferric chloride, cobaltous chloride, as generallyare other compounds with multivalent cations, such as calcium (Ca++),copper (Cu++), barium (Ba++), strontium (Sr++) and the like.

The time of gelation of the calcium alginate gels can be accomplished byregulating the concentration of free calcium ions in the solution.Typically the concentration of free calcium ions is controlled bymanipulation of the ionization rate of the calcium salt and/or by theinclusion of other compounds in the solution which react with the freecalcium ions.

Advantageously, it is possible to immobilize a wide range of activematerials, including non-water soluble materials as well as alcohols.

Preferred active materials entrained as droplets or microcapsules withinthe matrix are partially water-miscible organic molecules of compoundsthat have a molecular weight in the range of between about 100 to about400, preferably between about 150 to 300. The compounds contain aheteroatom that confers some degree of water-miscibility. For manycompounds of interest the sole heteroatom is oxygen, and there may be upto three heteroatoms per molecule in, for instance, hydroxy-substitutedor keto-substituted carboxylic acids. Unsubstituted carboxylic acids ofcourse contain two oxygen atoms and simple aldehydes, ketones and etherscontain only one oxygen atom. Compounds that contain nitrogen and/orsulphur atoms are also of interest.

Of particular interest are biologically active compounds. For purposesof the present invention, the term “biologically active” means materialsthat affect the life processes of organisms. Materials that arebiologically active include herbicides, pesticides, pharmaceuticals, andsemiochemicals, including naturally and artificially produced pheromonesand synthetic pheromone analogs. Materials of this nature that are ofparticular interest are those materials that interfere with a lifeprocess essential to the survival of a target pest.

The method of the invention can be used to immobilize pheromone withfunctional groups such as acetates, aldehydes, ketones, alcohols,esters, epoxies, ethers, or combinations thereof. Pheromones may bedefined as compounds which, when naturally produced, are secreted by onemember of an animal species which can influence the behaviour ordevelopment of another member of the same animal species. Pheromones arespecies-specific and therefore the application of pheromones for insectbehaviour modification has minimal effect on non-target pests.Pheromones supplied for modification of insect behaviour interfere withthe “mate finding process” by releasing point sources of pheromone,which may compete with or camouflage the pheromone plume of a female.This latter type of action differs from chemical insecticides or insectgrowth regulators or hormones, in that pheromones target futuregenerations of insects, not present ones. As pheromones are veryspecies-specific and are used only in small quantities, their use ismore environmentally acceptable than broadcasting of pesticides.

Many pheromones have an ester terminal group, for example and acetate orformate group. Typically these substances are water-immiscible andincorporation of them into microcapsules by known methods presents noparticular problem. Many other pheromones have an aldehyde or an alcoholterminal group. In general, these are partially water-miscible andpotentially reactive with the reactants used to encapsulate by prior,conventional methods. In particular, it is difficult to achieve highdegrees of encapsulation of materials that have some degree of watersolubility, as the material partitions between the small amount oforganic solvent and the relatively larger amount of water thatconstitutes the continuous phase. Furthermore, these compounds can beexpected to react with the reactants used to encapsulate. Aldehydes andketones react with amines to form aldimines and ketimines, respectively.Alcohols, carboxylic acids and mercaptans react with isocyanates. Epoxycompounds react both with amines and with isocyanates. Thus, the presentinvetion overcomes the limitation of delivering partially water-misciblesubstances such as alcohols, aldehydes, carboxylic acids, ketones,ethers, including epoxy compounds, and mercaptans.

Pheromones useful in the inventive microbeads are preferably insectpheromones. In describing the structure of the a pheromone, thefollowing notation is used: the type (E(trans)or Z(cis)) and position ofthe double bond or bonds are given first, the number of carbon atoms inthe chain is given next and the nature of the end group is given last.To illustrate, the pheromone Z-10 C19 aldehyde has the structure;

Pheromones can be mixtures of compounds with one component of themixture predominating, or at least being a significant component.Partially water miscible significant or predominant components of insectpheromones, with the target species in brackets, include, for example:E/Z-11 C14 aldehyde (Eastern Spruce Budworm), Z-10 C19 aldehyde (YellowHeaded Spruce Sawfly), Z-11 C14 alcohol (Oblique Banded Leafroller), Z-8C12 alcohol (Oriental Fruit moth) and E,E-8,10 C12 alcohol (Codlingmoth), E-11 C14 acetate (Sparganothis Fruitworm), and Z-11 C14 acetate(Blackheaded Fireworm).

An example of a ketone that is a pheromone is E or Z 7-tetradecen-2-one,which is effective with the oriental beetle. An ether that is not apheromone but is of value is 4-allylanisole, which can be used to renderpine trees unattractive to the Southern pine beetle.

Preferred embodiments of the invention are described with reference toimmobilization of partially water-miscible and water immisciblepheromones, but it should be appreciated that the invention extends toimmobilization of materials other than such pheromones and to microbeadscontaining materials other than pheromones. Those materials may, or maynot, be biologically active.

For example, alternatively, active materials containing mercaptans canbe immobilized in the microbeads of the invention, such as what is foundin urine of animals. These compounds are preferable in situations whereanimals mark their territory by means of urine, to discourage otheranimals from entering the particular territory. Examples of such animalsinclude preying animals such as wolves, lions, dogs, etc. By dispersinghydrogel microbeads containing the appropriate mercaptans, it ispossible to define a territory and discourage particular animals fromentering that territory. For example, the urine of a wolf includes amercaptan, and distribution of microbeads from which this mercaptan isgradually released to define a territory will discourage deer fromentering that territory. Other active materials useful in discouragingapproach of animals include essences of garlic, putrescent eggs andcapsaicin.

Other active compounds that can be included in the microbeads of theinvention include perfumes, fragrances, flavouring agents and the like.

Optionally, oil absorbents can be incorporated into the active droplets.These absorbents can help retain the active droplets within themicrobeads, resulting in longer lasting formulations. Clays and starchescould alternatively be used for this purpose.

The concentration of active material in the microbeads of the inventionshould be at a level such that the matrix forming material can stillprovide a strong, rupture resistant network and deliver an effectiveamount of the active material to the environment to which it isintended. Thus, the active material is preferably present in an amountbetween about 0.1 wt % to about 60 weight percent (wt %) of the totalweight of the microbead. More preferably, the amount of active materialis present in the microbead at between about 0.2 wt % to about 40 wt %;and most preferably between about 0.3 wt % to about 20 wt %.

The microbeads of the present invention are preferably delivered insuspension in aqueous or solvent-based solutions. For environmental andbiologically-friendly reasons, it is preferred that aqueous suspensionsbe used. Suspension aids are preferably included in the suspensionformulations to ensure the microbeads remain suspended in solution.

Preferably, the suspension solution is substantially free of monovalentcations, such as sodium, to avoid degradation or breakdown of themicrobeads. In a preferred aspect, a concentration of approximately 50millimolar of a crosslinker such as calium chloride is maintained in astored solution comprising the microbeads of the invention.

Optionally, adhesive material can be included in the compositions of theinvention to assist in retention of the microbeads to an intendedsubstrate. The adhesive material can be provided in various forms, suchas for example, latex or a tacky microspheres. Adherent propertiesimparted to the hydrogel microbeads should result in the microbeadsbeing able to still retain their suspended state and minimizeaggregation or coagulation in the aqueous suspension. Furthermore, anyadhesive material used to impart adherent properties should not affectthe integrity of the particles; it should not dissolve or weaken themicrobead(s).

A suitable adhesive material that may be included in the compositions ofthe invention is adhesive latex. The adhesive latex may be any suitablewater-dispersible adhesive available in the art. In the agriculturalbusiness, such latex compositions are often called stickers orspreaders. Stickers are used to help non-encapsulated agriculturechemicals adhere to plants. Spreaders are used to help dispersenon-encapsulated agriculture chemicals on application. Preferredadhesives are acrylate-based adhesives. One suitable latex is availablefrom Rohm & Haas under the trade designation COMPANION. Another isavailable from Deerpoint Industries under the trade designation DPIS-100 (a proprietary sticker/spreader). Examples of such adhesives arepolymers made from the “soft” monomers such as n-butyl acrylate,isooctyl acrylate, or the like, or copolymers made from a softcomponent, such as isobutylene, n-butyl acrylate, isooctyl acrylate,ethyl hexyl acrylate, or the like; and a polar monomer such as acrylicacid, acrylonitrile, acrylamide, methacrylic acid, methyl methacrylateor the like. Non-spherical polyacrylate adhesives are commerciallyavailable, for example, as the Rohm and Haas RHOPLEX line of adhesives.Preferably, the non-spherical polyacrylate adhesive is present in anamount of about 10-35% by weight of the total suspension.

Tacky microspheres of adhesive may alternatively be used to help adherethe hydrogel microbeads of the invention to an intended substrate. Thetacky microspheres have sufficient adhesive properties to provide thedesired adhesive function, yet there is no danger of completely coatingthe microbead which may lead to potentially inhibiting the releasecharacteristics of the microbead. The combination of microbeads andtacky microspheres may be applied without the need to modify theorifices of conventional sprayers with minimal clogging or pluggingproblems. Furthermore, the incorporation of tacky (adhesive)microspheres to the (formulation) suspension of microbeads allows themicrobeads' surfaces to become tacky. The beads can therefore stick tointended surfaces, such as, foliage and branches, for example. Theadhesive microspheres, especially if they are hollow, may also absorbsome of the active material into its own body, thus providing a secondmechanism of release of the active material. This could result in anoverall alteration, preferably an enhancement, of the release profile.

Preferably, the adhesive material is an acrylate- or methacrylate-basedadhesive system comprising infusible, solvent dispersible, solventinsoluble, inherently tacky, elastomeric copolymer microspheres asdisclosed in U.S. Pat. No. 3,691,140. Alternatively, this adhesivecomposition may comprise hollow, polymer, acrylate, infusible,inherently tacky, solvent insoluble, solvent dispersible, elastomericpressure-sensitive adhesive microspheres as disclosed in U.S. Pat. No.5,045,569. Other suitable adhesives are the tacky microspheres havingpendant hydrophilic polymeric or oligomeric moieties that are disclosedin U.S. Pat. No. 5,508,313.

Alternatively, the adhesive comprises between about 60-100% by weight ofhollow, polymeric, acrylate, inherently tacky, infusible,solvent-insoluble, solvent dispersible, elastomeric pressure-sensitiveadhesive microspheres having a diameter of at least 1 micrometer, andbetween about 0-40% by weight of a nonspherical polyacrylate adhesive.The hollow microspheres are made in accordance with the teaching ofEuropean Patent Application 371,635.

The compositions of the present invention may also include one or moreadjuvants including, for example, gelling aids, preservatives, dyes,humectants, fixatives, emulsifiers, extenders, and freeze/thawstabilizers such as polyhydric alcohols and their esters. Thesematerials are present in an amount effective to achieve their extendedfunction, generally less than about 5% typically less than 2%, by weightof the composition.

Incorporation of a light stabilizer can be included in the microbeads ofthe invention. Suitable light stabilizers include the tertiary phenylenediamine compounds disclosed in Canadian Patent No. 1,179,682, thedisclosure of which is incorporated by reference. The light stabilizercan be incorporated by dissolving it, with the active, in awater-immiscible solvent. Alternatively, a light stabilizer can beincorporated in the microbeads as taught in Canadian Patent No.1,044,134, the disclosure of which is also incorporated by reference.

Microencapsulated active materials are preferably formed usingconventional polyurea and/or polymethyleneurea encapsulation techniquessuch as what is taught in in U.S. Pat. Nos. 3,691,140; 5,045,569; and5,508313 as well as European Patent Application 371,365, all of whoseteachings are incorporated here by reference. Alternatively,microcapsules having gelatin shells may be used in the microbeads of theinvention and prepared by the methods provided in U.S. Pat. No.4,402,856. In another preferred embodiment, microcapsules mayalternatively be provided in the form of a liposome, and prepared by theprocesses taught in U.S. Pat. No. 4,911,928.

The process of making the microbeads of the invention, preferablycomprises, making the active filled microcapsules and dispersing themicrocapsule suspension in the hydrophilic matrix-forming material. Themixture is then hardened (gelled) to form microbeads. The resultingmicrobead is a hydrogel microbead, having greater than about 30% waterinitially, and the active-filled microcapsules would be dispersed andentrained within the water-polymer matrix.

The hydrophilic matrix with the microcapsules entrained in the matrixcan be formed either by ionic interactions or by thermal setting. Whenforming microbeads by ionic interactions, there are two preferredmethods of forming: (1) the spray method and (2) the emusificationmethod. In the spray method, the matrix-forming/active suspensionmixture is mixed and then atomized mechanically to form small sphericaldroplets. The size of the microbeads is generally governed by theintrinsic properties of the emulsion suspension, the feed rate and thecoaxial airflow rate.

The droplets which are atomized can then be allowed to free-falldirectly into a reacting bath. The reacting bath cures or sets thehydrogels so that they solidify. Reaction bath curing can be achievedthrough chemical or non-chemical means. For the case of sodiumalginates, calcium ions are used to cross-link the polymer chains. Apreferred crosslinker is calcium chloride.

Alternatively, an emulsification method can be used to produce hydrogelmicrobeads. In selecting the continuous phase material, it is preferablethat it be immiscible with the aqueous matrix forming material.

The matrix-forming material preferably has a range of concentrationsusable in practicing the invention. The concentration should be chosento optimize ease of handling, gelling time, the strength of the hydrogelmicrobead around the active material droplets. For example, a sodiumalginate solution can preferably be prepared in a concentration of about1 to about 10% (w/v) in water, more preferably about 1.5 to about 5% andmost preferably from about 1 to 3%. However, if the hydrogel agentconcentration is too great, the solution may be so viscous as to hinderthe formation of spherical microbeads.

Alternatively, hydrogel microbeads of the invention can be formed, forexample, by adding the matrix forming material solution drop-wise to aselected crosslinker. For example, a method can be used whereby dropletformation and crosslinker addition is completed as a one step process bya vibrating nozzle which ejects a hydrogel droplet from one source andcoats the droplet with a crosslinker from another. U.S. Pat. No.4,701,326 teaches use of this method.

In the preferred aspect where alginates are used to immobilize an activematerial, a crosslinker is preferably made up in solution at aconcentration of 1 to 1000 millimolar, more preferably 20 to 500millimolar and most preferably from 50 to 100 millimolar. Theconcentration ranges may have to be adjusted, depending on the nature ofa crosslinker and matrix-forming material.

The microbeads containing matrix material and active material can betreated with the crosslinker solution by soaking, spraying, dipping,pouring or any of sever other methods which will deposit an amount ofthe complexing agent on the droplet. When soaking, the time in solutionmay be from 1 second to 24 hours, preferably 1 minute to 1 hour, andmore preferably from 10 to 30 minutes.

The temperature for hydrogel microbead formation is preferably chosen asto avoid damage or alteration to the active material. For example, inthe preferred aspect where alginates are utilized, the temperature ispreferably in the range of about 1° C. to about 70° C.; more preferablybetween about 10° C. to about 40° C., and most preferably between about15° C. to about 30° C.

To immobilize active-filled microcapsules within a temperature settingmatrix, the matrix-forming material must first be solubilized in waterusing heat. The heating temperature is preferably be within a range ofabout 40° C. to about 100° C. When the matrix-forming material iscompletely dissolved, the temperature of the solution is lowered suchthat the solution is about 5° C. to about 10° C. above the gel settingtemperature. A suspension containing active-filled microcapsules is thenpreheated to a similar temperature to that of the matrix-formingsolution, afterwhich the two mixtures are blended together and mixedhomogeneously.

To produce the microbeads, the molten matrix-forming/microcapsulesuspension can be atomized through a nozzle system or be emulsifiedusing an oil type continuous phase. In the spray method, the moltensuspension can be atomized using coaxial air, for an example, anddropped into an ice bath containing distilled water. The matrix is thenformed, entraining the microcapsules therein.

To produce the microbeads using the emulsification method, a continuousoil phase is preheated in a jacketed reactor to the temperature of themolten microcapsule suspension. The continuous phase may be anyhydrophobic liquid. The preferred and most convenient liquid is avegetable oil or mineral oil. Other possible hydrophobic liquids mayinclude hydrofluorethers, siloxanes, or solvents such as cycloxhexanesand chloroforms. The microcapsule suspension is then emulsified in thecontinuous phase with the aid of a mixer. The mixing is continued untila desired particle size is obtained. The temperature of the reactionmixture is then lowered to that of ice water (about 5° C.). The matrixis then formed, entraining the microcapsules therein. The microbeads canthen be filtered and washed prior to suspending them in solution fordelivery.

Surfactants may be used in the process of forming the microbeads. Theincorporation of different surfactants will offer different types ofmicroemulsion drop sizes of the active within the hydrogel as well asdictate the amount of free oil lost in the reacting bath solution. Apreferred surfactant has a high critical micelle concentration, such asfor example, a product available under the product designation DISPONILSUS IC 875 (CMC˜1%), available from Henkel (Ambler, Pa.).

Particularly preferred surfactants are nonionic. Examples of suitablesurfactants include polyvinylpyrrolidone (PVP) andpoly(ethoxy)nonylphenol. PVP is usable and available at variousmolecular weights in the range of from about 20,000 to about 90,000. PVPhaving a molecular weight of about 40,000 is preferred.Poly(ethoxy)nonylphenols are commercially available under the tradedesignation IGEPAL from Rhone-Poulenc (Cranbury, N.J.), with variousmolecular weights depending on the length of the ethoxy chain.Poly(ethoxy)nonylphenols having the formula:

where n has an average value from about 9 to about 13 can be used. Apreferred poly(ethoxy)nonylphenols is available commercially under theproduct name IGEPAL 630, from Rhone-Poulenc (Cranbury, N.J.)—630 isindicative of the approximate molecular weight of the compound. Otherexamples of suitable surfactants include polyether block copolymers,such as those available under the trade designations PLURONIC andTETRONIC, both available from BASF (Washington, N.J.), polyoxyethyleneadducts of fatty alcohols, such as BRIJ surfactants available from ICI(Wilmington, Del.), and esters of fatty acids, such as stearates,oleates, and the like. Examples of such fatty acids include sorbitanmonostearate, sorbitan monooleate, sorbitan sesquioleate, and the like.Examples of the alcohol portions of the fatty esters include glycerol,glucosyl and the like. Fatty esters are commercially available assurfactants under the trade designation ARLACEL C from ICI (Wilmington,Del.)

Various properties of the surfactant, such as for example, chain length,functional groups, and hydrophobic regions, can affect the size of theactive droplets formed within the microbeads. For example, use of PVP(having a molecular weight of 40,000) tend to result in production oflarger sized active droplets than use of poly(ethoxy)nonylphenols(IGEPAL 630).

Ionic surfactants can alternatively be used in the processes of theinvention. Examples of suitable ionic surfactants partially neutralizedsalts of polyacrylic acids such as sodium or potassium polyacrylate orsodium or potassium polymethacrylate.

The microencapsulated active material entrained in the microbeads of theinvention are released gradually over time. This is a variant of themeachanism that could occur with conventional microencapsulatedmaterials that do not have a hydrophilic matrix to cushion and protectthe active, since an unprotected microcapule could potentially releasethe active ingredient nearly all at one time, for example at the time ofshell rupture. Active release from the microbeads of the invention ispreferably and advantageously controllable by controlling the humidity(and dryness) of the environment in which the microbeads are located.

While not being bound by this theory, it is believed that one mechanismof release of the active involves water evaporation from the gel matrixfollowed by the diffusion of active through the microcapsule shell ormembrane and then through the hydrophilic matrix. Release (diffusion) bythis mechanism could result in a delayed release of the active. Inanother theorized mechanism, the active becomes entrained in the waterfrom the matrix, and as the water evaporates, the active releases intothe atmosphere.

In preferred applications, these hydrogel microbeads would be sprayedfollowed by water evaporation within the gel. As the hydrogel beaddehydrates, the matrix shrinks in size and releases its active withtime. The degree of shrinkage of the microbead from its original size,depending on the components used in the formulation. Preferably, themicrobeads shrink about 10% to about 90% from its original size, morepreferably from about 40% to about 80%, and most preferably from about50% to about 70%.

Advantageously, the microbead, upon re-exposure to humidity, can swelland rehydrate itself by absorbing water. Re-exposure to humidity can beperformed in various ways. For example the microbeads' surfaces can becontacted directly with water or other aqueous solutions. Inagricultural applications where pheronomes are used as the activematerial, a farmer or caretake can irrigate the plants and foliage tore-hydrate the hydrogel microbeads. Alternatively, the humidity of theenvironment or ambient air in which the microbeads are located in can beincreased by entraining air droplets in the air. Thus, the microbeadscan be “re-activated” by re-hydration, thereby selectively controllingthe release times of the active material.

The microbeads of the invention can be delivered to an intendedsubstrated by various methods. In the preferred embodiment where theactive material is a pheromone, delivery of the microbeads will dependon various factors, such as for example, the size of release coveragedesired. For small concentrated areas, the microbeads can be impregnatedinto hollow fibres, plastic laminate flakes or twist-ties and thenphysically attaching the fibres or ties to plants to be protected frominsect infestation. For larger areas, spraying (aerially or byback-pack) may be the better option.

All patents cited in this specficiation are hereby incorporated byreference.

The following examples are for illustration purposes only and are notmeant to limit the scope of the invention. Unless otherwise specified,all parts and percentages are by weight.

EXAMPLES Preparatory Examples

The microencapsulation procedures disclosured in U.S. Pat. Nos.3,691,140; 5,045,569; and 5,508,313 and European Patent Application371,365 were followed to prepare microencapsulated active materials. Anaqueous suspension of microcapsules of each of the pheromones inPreparatory Samples A through C were encapsulated in a polyurea shell(50 g) and Rhamsan gum suspended suspending agent were added, withstirring. Discrete spherical microcapsules were produced with a sizerange of 10 to 100 microns and a mean diameter of about 50 microns.

Preparatory Sample A: Z7-Z11-C16 acetate and Z7-E11-C16 acetate (1:1)

Preparatory Sample B: E11-C14 acetate

Preparatory Sample C: E11-C14 alcohol

It was noted that the microcapsule shell wall of Sample C was not asstrong compared to microcapsules formed by Sample A & B. Microcapsulewalls of Sample C broke down once the water was evaporated away leavinga pool of pheromone.

Example 1

Microbeads Formed by Spray Method

A sodium alginate solution was initially prepared by dissolving apreweighed amount of alginate into a known volume of distilled water.The solution was mixed thoroughly to solubilize the polymer and wasdeaerated for removal of entrained air bubbles. In a separate 250 mLvessel, 80 g of a 2% alginate solution (SKW; Lannilis, France) was mixedwith 20 g of polyurea microcapsule suspension (Preparatory Sample B) ata speed of about 300 RPM using a marine type impeller (3 cm diameter).The microcapsule suspension was then atomized into fine particledroplets using a coaxial air nozzle sprayer into a calcium chloride bath(50 mM concentration). The size of the particles was determined by thesettings on the atomizing device. This involved control of the nozzlehead diameters, the feed rate of the emulsion through the nozzle and theairflow which passed along its feed path. At a nozzle feed diameter was0.508 mm, the coaxial air nozzle was 1.17 mm in diameter, the feedpressure was about 140 kPa, and the airflow was about 35 kPa fineparticles were formed. Discrete spherical microbeads having polyureamicrocapsules entrained in the alginate matrix were obtained, themicrobeads having a mean diameter of about 500 microns.

Example 2

Microbeads Containing Alcohol Type Pheromone Microcapsules

The procedure outline in EXAMPLE 1 was adopted and followed except thatthe microcapsules used were polyurea containing E11-C14 alcohol(Shin-Etsu Chemical Co., Ltd.; Tokyo, Japan) obtained from PreparatorySample C. The resulting microbeads were discrete and immobilized themicrocapsules without damaging the polyurea shell. Upon dehydration ofthe hydrogel, the alginate matrix appeared to envelope the polyureamicrocapsule such that the particles remained intact.

Example 3

Microbeads Using an Emulsification Method

An agarose solution (Aldrich Chemical Co.; Milwaukee, Wis.) wasinitially prepared by dissolving a preweighed amount of agarose into aknown volume of distilled water. The solution was mixed thoroughly tosolubilize the matrix forming solution by heating it to a temperature ofabout 100° C. The temperature of the matrix forming forming solution wasthen lowered until it approached the setting temperature (usuallybetween 40-70° C. depending on the polymer used). Equal weights of apolyurea microcapsule suspension containing pheromone (PreparatorySample A) was preheated to about 40-70° C. and mixed with the matrixforming solution while maintaing the temperature somewhere between40-70° C. 50 g of this warm microcapsule suspension was poured into a500 mL glass jacketed reactor set to a temperature of about 60° C.containing 200 g of light mineral oil (Drakeol 34; Penreco; Karns City,Pa.). The mixture was mixed at 600 RPM using a disc turbine agitator(5.08 cm diameter) for about 2 minutes. The emulsion was then quicklycooled in an ice bath for 10 minutes. The microbead diameter ranged insize from 0.1 to 1.5 mm. The resulting microbeads contained immobilizedmicrocapsules within a temperature setting agarose gel matrix.

Example 4

Microbeads Using an Emulsification Method

A carrageenan solution (SKW; Carenton, France) was initially prepared bydissolving a preweighed amount of K-carrageenan into a known volume ofdistilled water. The solution was mixed thoroughly to solubilize thematrix forming material by heating the solution to a temperature ofabout 80° C. Equal weights of a polyurea microcapsule suspensioncontaining pheromone (Prepraratory Sample A) was preheated to about 80°C. and mixed with the matrix forming solution while maintaing thetemperature at 80° C. 50 g of this warm microcapsule suspension waspoured into a 500 mL glass jacketed reactor set to a temperature ofabout 80° C. containing 200 g of light mineral oil (Drakeol). Themixture was mixed at 600 RPM using a disc turbine agitator (5.08 cmdiameter) for about 24 minutes. The emulsion was then quickly cooled inan ice bath for 10 minutes. 200 g of a 3% potassium chloride solutionwas added to the suspension to further cross-link the microbeads. Themicrobead diameter ranged in size from 0.1 to 1.5 mm. The resultingmicrobeads contained entrapped microcapsules within a temperaturesetting carageenan gel.

Example 5

Microbeads were made using coaxial airflow atomization, using theformulation of Example 2. Average particle particle diameters weremeasured by evaluating 30-50 microbeads, using a light microscope, LEITZDIAPLAN available from Ernst Leitz (Wetzlar, West Germany). Themicrobeads containing alcohol pheromone E11-C14 alcohol, obtained fromSample 2, were placed onto a microscope slide and microphotographed at amagnification of 40×. A digital image of the micrograph is provided inFIG. 2. As seen in FIG. 2, microbeads 20 comprise a matrix 22 havingactive-filled polyurea microcapsules 24 entrained in matrix 22. Afterexposing the microbeads to air at room temperature for about 8 hours,the same microbeads were microphotographed at the same magnification of40×. Referring now to FIG. 3, a digital image of the micrograph takenafter dehydration of the microbeads, it is shown that matrix 22 hasshrunk and shrouded around microcapsules 24, where microcapsules 24appear to be intact.

What is claimed is:
 1. A method of delivering and releasing activematerial, comprising the steps of: (a) providing gelled beads, saidbeads being a hydrophilic matrix having microcapsules entrained therein,said microcapsules comprising a pheromone; (b) creating a suspension ofa plurality of said beads; (c) delivering said suspension comprisingsaid beads to an intended environment; and (d) allowing said beads todehyhdrate.
 2. The method according to claim 1 further comprising thesteps of: (e) exposing said beads to humidity; and (f) allowing saidbeads to rehydrate.
 3. The method according to claim 2 wherein said stepof exposing said beads to humidity is performed by wetting the surfacesof said beads with a solution.
 4. The method according to claim 2wherein said step of exposing said beads to humidity is performed byadding moisture to the ambient air.
 5. The method according to claim 2wherein said steps c) thru e) are repeated sequentially.
 6. The methodaccording to claim 1 wherein said microcapsules are made from a materialselected from the group consisting of polyurea, polymethylenurea,polyurethane gelatin, and lipisome.
 7. The method according to claim 1wherein said microbeads further comprise a plurality of active materialdroplets.
 8. The method according to claim 1 wherein said hydrophilicmatrix is selected from the group consisting of a polysaccharide,polyvinyl alcohol, polyacrylamides, and methacrylates.
 9. The methodaccording to claim 8 wherein said matrix is a polysaccharide selectedfrom the group consisting of alginate, chitosan, carrageenan, gum andagar.
 10. The method according to claim 1 wherein said active materialis selected from the group consisting of a pheromone,mercaptan-containing compound, herbicide, pesticide, and pharmaceuticalmaterial.
 11. The method according to claim 1 wherein said hydrophilicmatrix is an alginate.
 12. The method according to claim 1 wherein saidbead has an average diameter between about 1 μm to about 1000 μm. 13.The method according to claim 1 wherein said bead has an averagediameter between about 1 μm to about 500 μm.
 14. The method according toclaim 1 wherein said bead further comprises a surfactant.
 15. The methodaccording to claim 1 wherein said bead further comprises an oilabsorbent.
 16. The method according to claim 1 wherein said beadsfurther comprise an additive selected from the group consisting ofpreservatives, humectants, stabilizers, UV protectants, and combinationsthereof.
 17. The method of claim 1 wherein said microcapsules arepresent in an amount between about 0.1 wt % to about 60 wt % of thetotal weight of said bead.
 18. The method of claim 1 wherein saidmicrocapsules are in an amount between about 0.2 wt % to about 40 wt %of the total weight of said bead.
 19. The method of claim 1 wherein saidmicrocapsules are present in an amount between about 0.3 wt % to about20 wt % of the total weight of said bead.
 20. The method of claim 1wherein said microcapsules have a diameter of about 0.01 nm to about 300μm.
 21. The method of claim 1 wherein said microcapsules have a diameterof about 0.05 nm to about 200 μm.
 22. A sprayable composition comprisingbeads suspended in a solution, wherein said beads comprise a hydrophilicmatrix having a plurality of microcapsules containing pheromoneentrained therein.
 23. The composition of claim 22 wherein the beadsfurther comprise active material droplets.
 24. The composition of claim22 further comprising adhesive material selected from the groupconsisting of hollow tacky adhesive microspheres, solid tacky adhesivemicrospheres, latex, and combinations thereof.
 25. The composition ofclaim 22 wherein said beads further comprise a surfactant.
 26. Thecomposition of claim 22 wherein said beads further comprise an oilabsorbent.
 27. The composition of claim 22 wherein said beads furthercomprise an additive selected from the group consisting ofpreservatives, humectants, stabilizers, UV protectants, and combinationsthereof.